Role of Enzymic Antioxidants in Mediating Oxidative Stress and Contrasting Wound Healing Capabilities in Oral Mucosal/Skin Fibroblasts and Tissues.

Unlike skin, oral mucosal wounds are characterized by rapid healing and minimal scarring, attributable to the "enhanced" healing properties of oral mucosal fibroblasts (OMFs). As oxidative stress is increasingly implicated in regulating wound healing outcomes, this study compared oxidative stress biomarker and enzymic antioxidant profiles between patient-matched oral mucosal/skin tissues and OMFs/skin fibroblasts (SFs) to determine whether superior oral mucosal antioxidant capabilities and reduced oxidative stress contributed to these preferential healing properties. Oral mucosa and skin exhibited similar patterns of oxidative protein damage and lipid peroxidation, localized within the lamina propria/dermis and oral/skin epithelia, respectively. SOD1, SOD2, SOD3 and catalase were primarily localized within epithelial tissues overall. However, SOD3 was also widespread within the lamina propria localized to OMFs, vasculature and the extracellular matrix. OMFs were further identified as being more resistant to reactive oxygen species (ROS) generation and oxidative DNA/protein damage than SFs. Despite histological evaluation suggesting that oral mucosa possessed higher SOD3 expression, this was not fully substantiated for all OMFs examined due to inter-patient donor variability. Such findings suggest that enzymic antioxidants have limited roles in mediating privileged wound healing responses in OMFs, implying that other non-enzymic antioxidants could be involved in protecting OMFs from oxidative stress overall.

Identification of a transcriptional signature for the wound healing continuum.

There is a spectrum/continuum of adult human wound healing outcomes ranging from the enhanced (nearly scarless) healing observed in oral mucosa to scarring within skin and the nonhealing of chronic skin wounds. Central to these outcomes is the role of the fibroblast. Global gene expression profiling utilizing microarrays is starting to give insight into the role of such cells during the healing process, but no studies to date have produced a gene signature for this wound healing continuum. Microarray analysis of adult oral mucosal fibroblast (OMF), normal skin fibroblast (NF), and chronic wound fibroblast (CWF) at 0 and 6 hours post-serum stimulation was performed. Genes whose expression increases following serum exposure in the order OMF < NF < CWF are candidates for a negative/impaired healing phenotype (the dysfunctional healing group), whereas genes with the converse pattern are potentially associated with a positive/preferential healing phenotype (the enhanced healing group). Sixty-six genes in the enhanced healing group and 38 genes in the dysfunctional healing group were identified. Overrepresentation analysis revealed pathways directly and indirectly associated with wound healing and aging and additional categories associated with differentiation, development, and morphogenesis. Knowledge of this wound healing continuum gene signature may in turn assist in the therapeutic assessment/treatment of a patient's wounds.

Hyaluronan facilitates transforming growth factor-beta1-mediated fibroblast proliferation.

This study aims to understand the role of the matrix polysaccharide hyaluronan (HA) in influencing fibroblast proliferation and thereby affecting wound healing outcomes. To determine mechanisms that underlie scarred versus scar-free healing, patient-matched dermal and oral mucosal fibroblasts were used as models of scarring and non-scarring fibroblast phenotypes. Specifically, differences in HA generation between these distinct fibroblast populations have been examined and related to differences in transforming growth factor-beta(1) (TGF-beta(1))-dependent proliferative responses and Smad signaling. There was a differential growth response to TGF-beta(1), with it inducing proliferation in dermal fibroblasts but an anti-proliferative response in oral fibroblasts. Both responses were Smad3-dependent. Furthermore, the two fibroblast populations also demonstrated differences in their HA regulation, with dermal fibroblasts generating increased levels of HA, compared with oral fibroblasts. Inhibition of HA synthesis in dermal fibroblasts was shown to abrogate the TGF-beta(1)-mediated induction of proliferation. Inhibition of HA synthesis also led to an attenuation of Smad3 signaling in dermal fibroblasts. Microarray analysis demonstrated no difference in the genes involved in TGF-beta(1) signaling between dermal and oral fibroblasts, whereas there was a distinct difference in the pattern of genes involved in HA regulation. In conclusion, these two distinct fibroblast populations demonstrate a differential proliferative response to TGF-beta(1), which is associated with differences in HA generation. TGF-beta(1) regulates proliferation through Smad3 signaling in both fibroblast populations; however, it is the levels of HA generated by the cells that influence the outcome of this response.

Chronic ulcers, calcification and calcified fibrous tumours: phenotypic manifestations of a congenital disorder of heterotopic ossification.

Calcification is a rarely reported cause for chronic, cutaneous ulceration. Although dystrophic calcification occurs in chronic ulcers, idiopathic calcification and ossification leading to recurrent ulcerations is seldom reported. This report illustrates a challenging case with various non healing wounds, calcification/ossification and calcified fibrous tumours. A 56-year-old woman presented with chronic, painful wounds and calcified deposits in her feet, hands and abdomen, some dating back to childhood. The surgeries she had had for various unrelated conditions healed with hard, calcified deposits, which later ulcerated. Skeletal radiological imaging revealed multiple soft-tissue deposits, with calcification and areas of ossification, along with gross distortion of the bony architecture of her feet. All biochemical investigations were normal apart from raised serum alkaline phosphatase. The management has encompassed a combination of conservative and surgical measures (culminating in a left below-knee amputation) with varying degrees of success. Having ruled out other causes of subcutaneous calcification, three congenital disorders of heterotopic ossification fit this patient's presentation: Albright hereditary osteodystrophy (AHO), fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH). Although AHO and FOP are possibilities, POH is most likely. In addition to describing the diverse phenotypic manifestations of this disorder, this report discusses the diagnostic dilemmas, difficulties in optimising the management plan and issues relating to health-related quality of life in this patient.

Effect of sharp debridement using curette on recalcitrant nonhealing venous leg ulcers: a concurrently controlled, prospective cohort study.

The objective of this study was to evaluate the effect of sharp debridement on the progression of recalcitrant chronic venous leg ulcers (CVLU) and to assess the feasibility of performing this procedure in an outpatient setting. We performed a prospective study of 55 CVLU (53 patients) over a 12-month period. The study group, which underwent debridement, contained 28 CVLU whose wound beds had slough, nonviable tissue, and no granulation tissue. The control group was 27 CVLU with minimal (15-20%) granulation tissue, but no slough or nonviable tissue. Treatments were otherwise similar. Age, body mass index, mean ulcer surface area (MSA) and mean ulcer duration were comparable in both groups. Ulcer measurements were taken at 4 weeks before debridement, at the time of debridement, and 4 and 20 weeks post-debridement. There was no change in the MSA from 4 weeks before to the time of debridement in either group. At 4 weeks post-debridement, the study ulcers showed a 6 cm(2) reduction in the MSA vs. a 1 cm(2) reduction in controls (P = 0.02). By week 20 post-debridement, the study ulcers achieved a 7.4 cm(2) reduction in the MSA vs. an increase of 1.3 cm(2) in controls (P = 0.008). Between weeks 8 and 20 post-debridement, 16% of study ulcers vs. 4.3% of control ulcers achieved complete healing. Infection rates and antimicrobial usage were similar. We conclude that sharp debridement is effective in stimulating healing of recalcitrant CVLU. It is safe, well tolerated, and can be performed in an outpatient setting.

Management of leiomyosarcomas of the spermatic cord: the role of reconstructive surgery.

BACKGROUND: Leiomyosarcomas (LMS) of the spermatic cord are extremely rare. Radical inguinal orchiectomy and high ligation of the cord is the standard primary surgical procedure. The extent of surrounding soft tissue excision required and the precise role of adjuvant radiotherapy, however, remains unclear. In addition, recurrence is a commonly encountered problem which might necessitate further radical excision of adjacent soft tissues. METHODS: This article reviews the pathophysiology of spermatic cord leiomyosarcomas (LMS), and discusses the various reconstructive surgical options available to repair the inguinal region and the lower anterior abdominal wall after excision of the tumour and the adjacent soft tissues. RESULTS: There is paucity of literature on LMS of spermatic cord. The majority of paratesticular neoplasms are of mesenchymal origin and up to 30% of these are malignant. In adults, approximately 10% of spermatic cord sarcomas are LMS. Approximately 50% of these tumours recur loco-regionally following definitive surgery; however, the incidence decreases if resection is followed by adjuvant radiotherapy. CONCLUSION: It is therefore important to achieve negative histological margins during the primary surgical procedure, even if adjuvant radiotherapy is instituted. If extensive resection is required, either during the primary procedure or following recurrence, reconstructive surgery may become necessary. This article reviews the pathophysiology of spermatic cord LMS, the reasons for recurrence, and discusses the management options including the role of reconstructive surgery.

Glass front of gas fire places: a clear and present danger.

BACKGROUND: Glass fronted gas fires have become a popular addition to many homes as a source of heat energy. The flames, however, provide curiosity for young children attracting them towards the hot glass plate resulting in contact burns. Our study aimed to ascertain the features and pattern of morbidity of such injuries, and to address preventive measures. METHODS: Retrospective analysis of children with contact burns who were treated in our unit over an eight-year period. The cases were identified from the burns database, and their case-notes and follow-up records reviewed. RESULTS: Thirty-five children (M: 20; F: 15; Age range: 6 months to 10 years) were identified. The total body surface area of the burn was between <1 and 5%. Hand or fingers were the commonest sites involved. The depth was variable with 21 children sustaining superficial and seven deep dermal burns. All but one child were treated conservatively. Follow-up visits ranged from one to 24 (median: five); follow-up period was from 2 days to 1 year (median: 17 days). CONCLUSION: Although glass plate contact burns may be minor and superficial, they nevertheless affect a vital anatomical area. They also result in psychological distress for the child, and stress and time off work for parents. Awareness and measures to prevent such injuries should therefore be addressed by the responsible authorities.

Dystrophic calcification as a cause for non healing leg ulcers.

Despite advances in molecular biology and a repertoire of other therapeutic options, chronic venous leg ulcers remain a significant problem within our society. There are various reasons, both local and systemic, which contribute to the non healing nature of such wounds. Among them, dystrophic calcification (DC) or calcified deposits within the ulcer bed, although rare, is an overlooked and a seldom reported cause. In the presence of DC, wound healing cannot proceed through a timely and orderly manner resulting in a non healing ulcer. In this article, we discuss the aetiology, pathophysiology and the management options of this rarely reported condition. We also report their clinical prognosis using a series of patients with venous ulcers complicated by DC leading to difficulties in healing.

Early diagnosis is vital in the management of squamous cell carcinomas associated with chronic non healing ulcers: a case series and review of the literature.

The association between chronic ulcers and squamous cell carcinomas (SCCs) is well established. Their clinical presentations, however, are varied, ranging from innocously appearing lesions to overtly exophytic growths. We present a series of cases with heterogeneous clinical presentations and different treatment outcomes. Case series - patient 1 was a 69-year-old man with an 18-month history of static non healing venous leg ulcer, but no sinister features, biopsy was performed to rule out Marjolin's transformation, histology revealed SCC and treatment was simple excision and skin grafting; patient 2 was a 73-year-old lady with an 18-month history of non healing ulcer (innocuous appearance) over distal interphalangeal joint of index finger, histology revealed SCC with deeper extension and treatment was amputation of distal half of finger; patient 3 was a 73-year-old lady with a 12-month history of non healing fungating leg ulcer with irregular borders and everted edges, histology revealed SCC (tumour eroding tibia and distant metastasis) and treatment was above-knee amputation, radiotherapy and palliation. Whilst SCC is amenable to simple excision in the early stages, delay in diagnosis could result in loss of the affected digit or limb; an SCC which has metastasised is also life threatening. Therefore, a low threshold to biopsy static non healing ulcers or ulcers in unusual sites should be adopted even in those not manifesting any evidence of malignancy.